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Interaction of monocytoid cells with the mucosal addressin MAdCAM‐1 via the integrins VLA‐4 and LPAM‐1
Author(s) -
YANG YI,
HARRISON JANE EB,
PRINT CRISTIN G,
LEHNERT KLAUS,
SAMMAR MAREI,
LAZAROVITS ANDREW,
KRISSANSEN GEOFFREY W
Publication year - 1996
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1038/icb.1996.67
Subject(s) - integrin , addressin , hl60 , cellular differentiation , biology , microbiology and biotechnology , promyelocyte , cell culture , retinoic acid , monocyte , myeloid , immunology , cell , biochemistry , genetics , gene
Summary The differentiation of myeloid cells into macrophages and granulocytes is accompanied by marked changes in adhesive phenotype. Here we seek to understand the regulation of expression and functionality of the VLA‐4 (α4βl). LPAM‐I (α4β7) and HML‐I (αEβ7) integrins on monocytes/macrophages and granulocytes, given that these integrins including LFA‐I (αLβ2) mediate the entry, retention and signalling events of pathogenic leucocytes within chronically inflamed tissues. Phorbol ester‐induced monocytic differentiation of the promyelocyte cell line HL60 led to increases in the steady‐state levels of β2 and β7 mRNA transcripts, requiring a period of 10 and 24 h. respectively, of de novo protein synthesis. There was a parallel de now expression of LPAM‐1 on the cell surface, despite the fact that a4 mRNA transcripts were rapidly down regulated. At 72 h. HML‐1 was not coexpressed with LPAM‐1 on HL60 cells, although it was weakly expressed on peripheral blood monocytes/macrophages after a prolonged period of in vitro culture. Retinoic acidinduced granulocytic differentiation of HL60 cells led to the appearance of low levels of LPAM‐1 at the cell surface. LPAM‐1 was not found expressed on peripheral blood neutrophils, raising the possibility that it is transiently expressed during granulocyte differentiation. In accord with the above findings, differentiated monocytes and HL60 cells bound to recombinant MAdCAM‐1 in an α4‐ and β7‐integrin‐dependent fashion, whereas a population of undifferentiated HL60 cells and Mn ++ ‐activated monocytes bound in an α4‐integrindependent β7‐integrin‐independent manner via VLA‐4 expressed abundantly at all stages of differentiation. Four h after attachment, some of these VLA‐4 + LPAM‐1 ‐ HL60 cells could be seen to start spreading. These findings suggest that MAdCAM‐l can bind to VLA‐4 when LPAM‐1 is absent, and thus has the potential to recruit both VLA‐4‐bearing monocytes and VLA‐4 + LPAM‐1 + macrophages into chronically inflamed tissues.